Shiga toxin B chain is the binding subunit of the toxin, which has been purified and the amino acid sequence of this 6,500 dalton polypeptide was recently determined.
Vaccination against the Shigella bacillus and shigellosis presents several problems that have not been overcome in spite of many efforts. Some of the difficulties are inherent to the system of shigellosis. Pathogenesis in this case is generally considered to be related to the invasive properties of the organism (Genski, P et al., J. Infect. Dis 126:523 (1972)), the most clinically virulent species of which is Shigella dysenteria l (the Shiga bacillus). Most of the attempts towards Shigella vaccine preparation have been based on the expression of virulence-associated membrane antigens. Pathogenic strains of Shigella are known to produce a toxin, the role of which in the pathogenesis of shigellosis is rather controversial. However, the existence of toxin-neutralizing antibodies in the sera of convalescent patients may be indicative of the possibility to employ the toxin or its derivatives for introducing a protective immunity.
The toxin of Shigella dysenteria l (the "Shiga toxin") is known as one of the most potent of the lethal microbial toxins. It is classified as a neurotoxin due to its activity when parenterally administered to sensitive animals. It is also cytotoxic to certain tissue culture cells, as well as enterotoxic when applied to intestinal mucosa. This toxin has been purified and its structure was characterized as comprising two subunits, A and B, of Mr32,000 and Mr6,500, respectively (Donohue-Rolfe et al., J. Exp. Med. 160:1767 (1984)). Antibodies raised against the B subunit neutralized the cytotoxic effects of the toxin in HeLa cells monolayers and also inhibited the binding of labeled toxin to these cells, indicating that the B subunit is involved in the Shigella toxin binding to cell surface, see above reference.
In recent years it has been demonstrated that synthetic peptides corresponding to fragments of some bacterial toxins, when attached to appropriate carriers, can induce neutralizing an immune response towards the native toxin. This was shown for diphtheria toxin and for cholera toxin. In the latter case the antibodies elicited by a 15 amino acid residue fragment of the toxin's B chain neutralized also the heat-labile toxin of E. coli, which is homologous in its sequence to the cholera toxin.